Germfree, colostrum-deprived piglets obtained by aseptic hysterectomy from specific pathogen-free Minnesota miniature swine are immunologically "virgin" as indicated by the absence of immunoglobulin and "background" antibody-forming cells. They are, however, immunologically competent as demonstrated by the excellent antibody response upon antigenic stimulation. The immunologically "virgin" piglets in the absence of passive maternal antibodies are extremely susceptible to microbial infections. However, they were completely protected when these piglets were fed 10 ml of colostrum or sow serum. We have found that preexisting "natural" antibodies are not required for the induction of the immune response, and also that they regulate the immune response. This suggests that maternal "natural" antibodies are not only required to protect from microbial infection but also play a role in the regulation of the immune system of neonates. This unique immunologically "virgin" piglet model will be used to investigate further the significance of passive maternal "natural" antibodies on the development of the immune system of the young, specifically: (1) protective role of maternal "natural" antibodies for suckling's survival; define immunoglobulin classes of "natural" antibodies for systemic and local defense mechanisms; (2) the relationship of the immune system and intestinal permeability to macromolecules; mechanisms of intestinal absorption and termination absorption; (3) the cellular nature of the effector cells and role of maternal "natural" antibodies on cellular natural killer (CNK) cells and/or the killer (K) cells of antibody-dependent cellular cytotoxicity (ADCC) of the neonates, and the study of the ontogeny of the CNK and/or K cells; and (4) immunoregulatory function of maternal "natural" antibodies on the development of active immunity of the young. Studies with this unique system will provide basic knowledge on the immunology of maternal-feto/postnatal relationships and hopefully lead to better control or manipulation of the development of the immune system for sound child health.